P17 - LYSYL OXIDASES: EMERGING PROMOTERS OF SENESCENCE ESCAPE, TUMOR INITIATION AND PROGRESSION

Abstract

Lysyl oxidase activity, exhibited by five lox members, has been extensively associated with tumor progression and metastasis. Notably, it is well documented that lox factors, mainly LOX and LOXL2 proteins, are implicated in invasion, cell migration, and angiogenesis in response to tumor-associated hypoxia. In the clinic, their expression correlates with bad prognosis for cancer progression and patient survival. Recently, lox factors have been observed to promote senescence escape, a critical event in tumorigenesis. In two mouse cancer susceptibility models for breast and pancreatic cancer, LOX and/or LOXL2 were found to promote tumorigenesis in cooperation with an oncogenic signal. Mechanistically, lox factors might mediate their effects via several mechanisms; from reorganizing the extracellular matrix and tumor microenvironment, promoting activation of specific pathways such as FAK and Akt pathways, to regulating gene expression by modifying the histone tails on specific target genes such as E-cadherin. This modification impacts the epithelial-mesenchymal transition, a process involved in senescence escape, tumor initiation and progression. The recent literature highlights an important role of lox factors in cancer, and an antibody directed against LOXL2 is already undergoing clinical trials. A better understanding of the biology of these factors will help the design and application of new lox-derived therapeutic tools.